ArticleGenes & development2006
Proteolysis of MLL family proteins is essential for taspase1-orchestrated cell cycle progression.
Article in Genes & development, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 173 citations in OpenAlex.
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- KMT2A-rearranged leukemia: from mechanism to drug development.Experimental hematology · 2025Review
- PRMT1-mediated methylation regulates MLL2 stability and gene expression.Nucleic acids research · 2025Article
- Histone lysine methylation modifiers controlled by protein stability.Experimental & molecular medicine · 2024Review
- Multi-omics analysis of a case of congenital microtia reveals aldob and oxidative stress associated with microtia etiology.Orphanet journal of rare diseases · 2024Article
- Unveiling the Molecular Landscape of Pancreatic Ductal Adenocarcinoma: Insights into the Role of the COMPASS-like Complex.International journal of molecular sciences · 2024Review
- KMT2 Family of H3K4 Methyltransferases: Enzymatic Activity-dependent and -independent Functions.Journal of molecular biology · 2024Review
- The Core Complex of Yeast COMPASS and Human Mixed-Lineage Leukemia (MLL), Structure, Function, and Recognition of the Nucleosome.Sub-cellular biochemistry · 2024Review
- Article
- Dual activity inhibition of threonine aspartase 1 by a single bisphosphate ligand.RSC advances · 2022Article
- Suleiman-El-Hattab syndrome: a histone modification disorder caused by TASP1 deficiency.Human molecular genetics · 2022Article
- The Taspase1/Myosin1f-axis regulates filopodia dynamics.iScience · 2022Article
- Direct targeted therapy for MLL-fusion-driven high-risk acute leukaemias.Clinical and translational medicine · 2022Article
- Review
- Clinical Utility of a Unique Genome-Wide DNA Methylation Signature forInternational journal of molecular sciences · 2022Article
- A Bivalent Supramolecular GCP Ligand Enables Blocking of the Taspase1/Importin α Interaction.ChemMedChem · 2022Article
- Closantel is an allosteric inhibitor of human Taspase1.iScience · 2021Article
- Structure, Activity and Function of the MLL2 (KMT2B) Protein Lysine Methyltransferase.Life (Basel, Switzerland) · 2021Review
- Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates by cleaving TFIIA.JCI insight · 2021Article
- Deubiquitinating enzyme inhibitor alleviates cyclin A1-mediated proteasome inhibitor tolerance in mixed-lineage leukemia.Cancer science · 2021Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Taspase1 was identified as the threonine endopeptidase that cleaves mixed-lineage leukemia (MLL) for proper Hox gene expression in vitro. To investigate its functions in vivo, we generated Taspase1(-/-) mice. Taspase1 deficiency results in noncleavage (nc) of MLL and MLL2 and homeotic transformations. Remarkably, our in vivo studies uncover an unexpected role of Taspase1 in the cell cycle. Taspase1(-/-) animals are smaller in size. Taspase1(-/-) mouse embryonic fibroblasts (MEFs) exhibit impaired proliferation, and acute deletion of Taspase1 leads to a marked reduction of thymocytes. Taspase1 deficiency incurs down-regulation of Cyclin Es, As, and Bs and up-regulation of p16(Ink4a) . We show that MLL and MLL2 directly target E2Fs for Cyclin expression. The uncleaved precursor MLL displays a reduced histone H3 methyl transferase activity in vitro. Accordingly, chromatin immunoprecipitation assays demonstrate a markedly decreased histone H3 K4 trimethylation at Cyclin E1 and E2 genes in Taspase1(-/-) cells. Furthermore, MLL(nc/nc;2nc/nc) MEFs are also impaired in proliferation. Our data are consistent with a model in which precursor MLLs, activated by Taspase1, target to Cyclins through E2Fs to methylate histone H3 at K4, leading to activation. Lastly, Taspase1(-/-) cells are resistant to oncogenic transformation, and Taspase1 is overexpressed in many cancer cell lines. Thus, Taspase1 may serve as a target for cancer therapeutics.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.